Investigating key clinical aspects of Fibrous dysplasia of bone in a transgenic mouse model (EF1a-GsαR201C mice) of the disease: pain, effect of anti-resorptive treatments and “rebound” phenomenon.
Awardee: Mara Riminucci
Institution: Department of Molecular Medicine, Sapienza University of Rome
Grant Amount: $80,000.00
Funding Period: February 1, 2023 - January 31, 2024
Summary:
We will continue our studies on the link between bone resorption and bone pain in Fibrous dysplasia (FD) of bone. Thanks to our MDBR-21-110-FD award we set up in our laboratory three tests widely used to evaluate the presence of pain in mice (pain-like behavior) and, through these tests, we have demonstrated that our FD transgenic mice are a good model to study bone pain associated with FD. Then we have demonstrated that treatments that inhibit bone resorption [anti-mouse RANKL antibody (an equivalent of denosumab) and Zoledronic acid (a potent bisphosphonate)] improved mouse behavior in the different tests, thus suggesting a reduction of bone pain. In this project we will continue these studies and will analyzed the distribution of nerve fibers (involved in pain transmission) within FD lesions. In addition, we will start to analyze the mechanisms that underlie the reappearance of FD lesions in mice after anti-mouse RANKL antibody withdrawn, to better understand the “rebound” that occurs after denosumab discontinuation.